Diagnosis Of Primary Progressive Aphasia Research Articles

Clinical and Linguistic Profiles and Challenges in Diagnosis of Primary Progressive Aphasia in Medan, Indonesia: A Hospital-based Study

Background Primary Progressive Aphasia (PPA) is a degenerative condition characterized by progressive loss of language function. Studies on PPA patients in Indonesia are still limited, and none has reported clinical and linguistic profiles of PPA patients who speak Bahasa Indonesia. This study aimed to describe clinical and linguistic profiles and challenges in the diagnosis of PPA patients from referral hospitals in Medan, Indonesia. Methods We retrospectively reviewed the clinical records of patients diagnosed with PPA based on the 2011 diagnostic criteria during the 2022-2023 period and described clinical characteristics data and linguistic profiles using descriptive analysis. Results We included 6 cases that fulfilled the diagnostic criteria for PPA. There were 3 cases categorized as nfvPPA, 1 case as svPPA, and 2 cases as lvPPA. There was female predominance (83.3%) and the mean age at onset was 59±2.96 years. The first symptom reported in the nfvPPA group was effortful, non-fluent speech; in svPPA, it was impaired naming and single word comprehension, while in lvPPA, it was impairment in word retrieval. Challenges in diagnosis included the availability of a standardized language tool aimed specifically for PPA in Bahasa Indonesia and the expertise needed to make such a diagnosis. Conclusion The main clinical features of the PPA reported were similar to previous findings with specific characteristics of Bahasa Indonesia. Determining language profiles of each variant of PPA in Bahasa Indonesia is crucial to establishing a correct diagnosis. Language assessment tool in Bahasa Indonesia is urgently needed to facilitate better assessment and management planning to improve quality of life.

Utility of visual rating scales in primary progressive aphasia

IntroductionDifferential diagnosis among subjects with Primary Progressive Aphasia (PPA) can be challenging. Structural MRI can support the clinical profile. Visual rating scales are a simple and reliable tool to assess brain atrophy in the clinical setting.The aims of the study were to establish to what extent the visual rating scales could be useful in the differential diagnosis of PPA, to compare the clinical diagnostic impressions derived from routine MRI interpretations with those obtained using the visual rating scale and to correlate results of the scales in a voxel-based morphometry (VBM) analysis.MethodPatients diagnosed with primary progressive aphasia (PPA) according to current criteria from two centers—Ospedale Maggiore Policlinico of Milan and Hospital Clínic de Barcelona—were included in the study. Two blinded clinicians evaluated the subjects MRIs for cortical atrophy and white matter hyperintensities using two protocols: routine readings and the visual rating scale. The diagnostic accuracy between patients and controls and within PPA subgroups were compared between the two protocols.ResultsOne hundred fifty Subjects were studied. All the scales showed a good to excellent intra and inter-rater agreement. The left anterior temporal scale could differentiate between semantic PPA and all other variants.The rater impression after the protocol can increase the accuracy just for the logopenic PPA. In the VBM analysis, the scores of visual rating scales correlate with the corresponding area of brain atrophy.ConclusionThe Left anterior temporal rating scale can distinguish semantic PPA from other variants. The rater impression after structured view improved the diagnostic accuracy of logopenic PPA compared to normal readings. The unstructured view of the MRI was reliable for identifying semantic PPA and controls. Neither the structured nor the unstructured view could identify the nonfluent and undetermined variants.

Explainable machine learning radiomics model for Primary Progressive Aphasia classification.

Primary Progressive Aphasia (PPA) is a neurodegenerative disease characterized by linguistic impairment. The two main clinical subtypes are semantic (svPPA) and non-fluent/agrammatic (nfvPPA) variants. Diagnosing and classifying PPA patients represents a complex challenge that requires the integration of multimodal information, including clinical, biological, and radiological features. Structural neuroimaging can play a crucial role in aiding the differential diagnosis of PPA and constructing diagnostic support systems. In this study, we conducted a white matter texture analysis on T1-weighted images, including 56 patients with PPA (31 svPPA and 25 nfvPPA), and 53 age- and sex-matched controls. We trained a tree-based algorithm over combined clinical/radiomics measures and used Shapley Additive Explanations (SHAP) model to extract the greater impactful measures in distinguishing svPPA and nfvPPA patients from controls and each other. Radiomics-integrated classification models demonstrated an accuracy of 95% in distinguishing svPPA patients from controls and of 93.7% in distinguishing svPPA from nfvPPA. An accuracy of 93.7% was observed in differentiating nfvPPA patients from controls. Moreover, Shapley values showed the strong involvement of the white matter near left entorhinal cortex in patients classification models. Our study provides new evidence for the usefulness of radiomics features in classifying patients with svPPA and nfvPPA, demonstrating the effectiveness of an explainable machine learning approach in extracting the most impactful features for assessing PPA.

Speech and Language characteristics of Kannada and Hindi speaking individuals with Primary Progressive Aphasia

AbstractBackgroundLinguistic typology plays an important role in identifying clinical markers of language deficits that characterise Primary Progressive Aphasia (PPA). The current International criteria to diagnose PPA were primarily developed for English. Typological characteristics of Indian languages however differ from English in their morpho‐syntactic complexity, a flexible‐word order, richer morphology, ‘pro‐drop’ languages with absence of prepositions and transparent orthography. We aimed to develop a novel test in Kannada (Dravidian) and Hindi (Indo‐Aryan) to identify language deficits in Indian language speakers with PPA.MethodThe speech‐language test systematically developed for Kannada and Hindi consisted of unique tasks for syntax, semantics, phonology, motor speech and working memory. Participants underwent assessment of cognition and language with Addenbrooke’s Cognitive Examination‐III, Western Aphasia Battery‐Revised and Indian Semantic Memory Battery (ISMB) in addition to the novel test.ResultsOf 26 patients with PPA (Kannada 13, Hindi 13), 15 had non‐fluent variant (nfvPPA), 8 semantic variant (svPPA) and 3 logopenic variant (lvPPA). On the novel test, PPA had higher phonological, motor speech, syntactic and semantic errors compared to 60 controls. nfvPPA had higher phonological, motor speech and syntactic errors and lesser semantic errors compared to svPPA. Semantic and working memory errors discriminated between nfvPPA and svPPA. On qualitative analysis, 5 patients of nfvPPA had significant apraxia of speech. The other 10 had a unique syntactic profile: agrammatism was not prominent in their spontaneous speech and picture description. Sentences were relatively fluent, complete and sufficient for functional communication. The consistent abnormality observed was a reduction in overall length of utterance. Agrammatisms such as inappropriate use of case markers were restricted to specific tests of syntax. svPPA patients had increased verbal output and prominent paragrammatisms. Testing for surface dyslexia was not relevant due to the orthographic transparency of Indian languages.ConclusionThe novel language test for evaluation of Indian speakers of PPA revealed unique findings for diagnosis of nfvPPA. Reduction in length of utterances and lack of prominent agrammatism was a consistent clinical marker and owes itself to morpho‐syntactic complexity of Indian languages. Our study emphasises the need to account for linguistic typology in diagnosis of PPA.

Amygdalar pathology in early neuropsychiatric phenotypes due to 3R‐Pick disease

AbstractBackgroundPersons with dementia syndromes such as primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD) often develop neuropsychiatric symptoms (NPS). Various neurodegenerative diseases may cause PPA or bvFTD, including frontotemporal lobar degeneration (FTLD) with 3‐repeat tau pathology (Pick disease, “PiD”). Limbic regions implicated in mood and behavior, such as the amygdala, are highly impacted in FTLD with PiD. This study quantified Pick bodies and activated microglia in the amygdala of individuals with antemortem diagnosis of PPA or bvFTD and postmortem PiD neuropathology and examined associations with initial NPS.MethodWe identified 16 right‐handed cases from the Northwestern University Alzheimer’s Disease Research Center brain bank with bvFTD (N = 8) or PPA (N = 8) due to PiD with unilateral amygdala tissue (basolateral region) available. Fifteen cases had data on 12 NPS assessed via the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q) from their earliest visit. We performed AT‐8 or HLA‐DR immunohistochemistry on amygdala sections to visualize Pick bodies or HLA‐DR+ activated microglia, respectively. We quantified the density of Pick bodies per mm3 via modified unbiased stereology and used HALO software (Indica Labs) to quantify percent area of HLA‐DR immunopositivity. We assessed differences between clinical groups via Welch’s t‐test (Pick bodies) or repeated‐measures two‐way ANOVA (HLA‐DR). Pearson clinicopathologic correlations were examined between Pick bodies or HLA‐DR immunopositivity and initial endorsement of total (out of 12) or behavioral/comportmental (apathy, disinhibition, motor stereotypies, or appetite disturbance) NPI‐Q symptoms.ResultAmygdalar Pick body densities were similar between PPA (M = 28,822/mm3) and bvFTD (M = 29,114/mm3) cases. Compared to bvFTD, PPA cases trended towards a lower percent area of HLA‐DR immunopositivity (5.54% vs. 2.39%, p<0.10). There was no significant relationship between Pick Body density and initial NPIQ symptoms endorsed across all cases. However, area of HLA‐DR immunopositivity was positively correlated with initial endorsement of total (r = 0.47, p<0.10) and behavioral/comportmental (r = 0.54, p<0.05) NPI‐Q symptoms.ConclusionOur findings suggest that microglial pathology in the amygdala contributes to early neuropsychiatric presentations in PiD, particularly symptoms reflective of behavioral/comportmental disturbance. Future study will investigate the impact of neuronal size and density in the amygdala on NPS in these dementia syndromes due to PiD.

Assessment tools accuracy for classification and diagnosis of Primary Progressive Aphasia: A systematic review and meta-analysis protocol.

Introduction. Primary Progressive Aphasia (PPA) is a syndrome characterized by progressive decline in language function. There are three main PPA syndromes, each one features different language profiles and neuropathologic substrates. Although there are current clinical diagnostic criteria for PPA categorization, the utility of these requires evaluation(s) by specialized staff and the administration of extensive cognitive batteries. A diagnostic tool for PPA is not currently standardized, though some batteries have been developed and/or validated exclusively for PPA categorization. We aim to describe which cognitive/aphasia diagnostic tool has the best accuracy for PPA diagnosis and categorization. Methods and Analysis. MEDLINE (PubMed), EMBASE and Web of Science databases will be searched using adequate search strategies. Studies including original data of possible, probable, and definite PPA cases according to current clinical diagnostic criteria for PPA will be included. Inclusion criteria will be 1) Studies describing data of a cognitive/aphasia clinical battery including at least one test measure (e.g., specificity, positive predictive values, etc.) and 2) PPA diagnosis according to current clinical criteria as the reference standard. Two reviewers will perform the screening and data extraction. Quality assessment will be performed according to the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) guidelines. This systematic review protocol is reported as stated by with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) 2015 statement. Dissemination. Findings of this systematic review protocol will be disseminated through a publication in a peer-reviewed journal. Results will be helpful to improve the diagnosis and classification of PPA syndromes.

A cognitive marker for Alzheimer disease pathology in primary progressive aphasia? A validation study in the clinical setting

We validated in the clinical setting a putative clinical marker for a biological diagnosis of primary progressive aphasia (PPA) due to amyloid previously identified in an autopsy cohort and including impaired (score ≤4) digit span (DS) as index of phonological loop dysfunction and broadened criteria for logopenic PPA. In 29 PPA patients with an amyloid-positive (A+) biomarker and 28 PPA patients with an amyloid-negative (A−) biomarker, Receiver Operating Characteristics (ROC) curve analysis showed moderate specificity (71%) but insufficient sensitivity (41%) for the proposed marker. Specificity was particularly poor (58%) for the discrimination between A+ PPA and the A− subgroup with nonfluent PPA. DS may be compromised in both logopenic and nonfluent PPA, whose loci of neurodegeneration lie at the 2 ends of the left fronto-parieto-temporal system that underpins phonology. An Statistical Parametric Mapping (SPM) correlation analysis between DS score and metabolism on brain 18-fluoro-deoxy-glucose positron emission tomography also showed a major contribution of the left frontal cortex to impaired span.

Rare exonic variant affects GRN splicing and contributes to frontotemporal lobar degeneration

Heterozygous loss-of-function (LOF) mutations in the progranulin gene (GRN) cause frontotemporal lobar degeneration (FTLD) by a mechanism of haploinsufficiency. For most missense mutations, the contribution to FTLD is however unclear. We studied the pathogenicity of rare GRN missense mutations using patient biomaterials. We identified a new mutation in GRN, c.1178 A>C, in a patient with a diagnosis of primary progressive aphasia. Neuropathological examination of autopsied brain showed FTLD with TAR DNA-binding protein 43 (FTLD-TDP) type A pathology with concomitant Alzheimer’s disease pathology. Serum progranulin protein levels were reduced to levels comparable to known LOF mutations. The mutation is in the last codon of exon 10, in the splice donor sequence. Our data provide evidence that the mutation leads to aberrant splicing, resulting in a frameshift (p.(Glu393AlafsTer31)) and consequently nonsense-mediated mRNA decay. Our finding demonstrates that carefully examining sequencing data around splice sites is needed since this mutation was annotated as a missense mutation. Unraveling the pathogenicity of variants of unknown significance is important for clinical diagnosis and genetic counseling.

Speech Motor Profiles in Primary Progressive Aphasia.

Previous research on motor speech disorders (MSDs) in primary progressive aphasia (PPA) has largely focused on patients with the nonfluent/agrammatic variant of PPA (nfvPPA), with few systematic descriptions of MSDs in variants other than nfvPPA. There has also been an emphasis on studying apraxia of speech, whereas less is known about dysarthria or other forms of MSDs. This study aimed to examine the qualitative and quantitative characteristics of MSDs in a prospective sample of individuals with PPA independent of subtype. We included 38 participants with a root diagnosis of PPA according to current consensus criteria, including one case with primary progressive apraxia of speech. Speech tasks comprised various speech modalities and levels of complexity. Expert raters used a novel protocol for auditory speech analyses covering all major dimensions of speech. Of the participants, 47.4% presented with some form of MSD. Individual speech motor profiles varied widely with respect to the different speech dimensions. Besides apraxia of speech, we observed different dysarthria syndromes, special forms of MSDs (e.g., neurogenic stuttering), and mixed forms. Degrees of severity ranged from mild to severe. We also observed MSDs in patients whose speech and language profiles were incompatible with nfvPPA. The results confirm that MSDs are common in PPA and can manifest in different syndromes. The findings emphasize that future studies of MSDs in PPA should be extended to all clinical variants and should take into account the qualitative characteristics of motor speech dysfunction across speech dimensions. https://doi.org/10.23641/asha.22555534.

Structural correlates of language processing in primary progressive aphasia.

Understanding the relationships between brain structure and language behaviour in primary progressive aphasia provides crucial information about these diseases' pathomechanisms. However, previous investigations have been limited from providing a statistically reliable view of broad language abilities by sample size, variant focus and task focus. In this study, the authors aimed to determine the relationship between brain structure and language behaviour in primary progressive aphasia, to determine the degree to which task-associated regions were atrophied across disease variants and to determine the degree to which task-related atrophy overlaps across disease variants. Participants were 118 primary progressive aphasia patients and 61 healthy, age-matched controls tested from 2011 to 2018 in the German Consortium for Frontotemporal Lobar Degeneration cohort. Diagnosis of primary progressive aphasia required progressive deterioration of mainly speech and language for ≥ 2 years, and variant was diagnosed by the criteria of Gorno-Tempini et al. (Classification of primary progressive aphasia and its variants. Neurology. 2011;76(11):1006-1014). Twenty-one participants not fulfilling a specific subtype were classified as mixed-variant and excluded. Language tasks of interest included the Boston naming test, a German adaptation of the Repeat and Point task, phonemic and category fluency tasks and the reading/writing subtest of the Aachen Aphasia Test. Brain structure was measured by cortical thickness. We observed networks of language task-associated temporal, frontal and parietal cortex. Overlapping task-associated atrophy was observed in the left lateral, ventral and medial temporal lobes, middle and superior frontal gyri, supramarginal gyrus and insula. Some regions, primarily in the perisylvian region, were associated with language behaviour despite showing no significant atrophy. The results crucially extend less powerful studies associating brain and language measures in primary progressive aphasia. Cross-variant atrophy in task-associated regions suggests partially shared underlying deficits, whereas unique atrophy reinforces variant-specific deficits. Language task-related regions that are not obviously atrophied suggest regions of future network disruption and encourage understanding of task deficits beyond clearly atrophied cortex. These results may pave the way for new treatment approaches.

Genetic forms of primary progressive aphasia within the GENetic Frontotemporal dementia Initiative (GENFI) cohort: comparison with sporadic primary progressive aphasia.

Primary progressive aphasia is most commonly a sporadic disorder, but in some cases, it can be genetic. This study aimed to understand the clinical, cognitive and imaging phenotype of the genetic forms of primary progressive aphasia in comparison to the canonical nonfluent, semantic and logopenic subtypes seen in sporadic disease. Participants with genetic primary progressive aphasia were recruited from the international multicentre GENetic Frontotemporal dementia Initiative study and compared with healthy controls as well as a cohort of people with sporadic primary progressive aphasia. Symptoms were assessed using the GENetic Frontotemporal dementia Initiative language, behavioural, neuropsychiatric and motor scales. Participants also underwent a cognitive assessment and 3 T volumetric T1-weighted MRI. One C9orf72 (2%), 1 MAPT (6%) and 17 GRN (44%) symptomatic mutation carriers had a diagnosis of primary progressive aphasia. In the GRN cohort, 47% had a diagnosis of nonfluent variant primary progressive aphasia, and 53% had a primary progressive aphasia syndrome that did not fit diagnostic criteria for any of the three subtypes, called primary progressive aphasia-not otherwise specified here. The phenotype of the genetic nonfluent variant primary progressive aphasia group largely overlapped with that of sporadic nonfluent variant primary progressive aphasia, although the presence of an associated atypical parkinsonian syndrome was characteristic of sporadic and not genetic disease. The primary progressive aphasia -not otherwise specified group however was distinct from the sporadic subtypes with impaired grammar/syntax in the presence of relatively intact articulation, alongside other linguistic deficits. The pattern of atrophy seen on MRI in the genetic nonfluent variant primary progressive aphasia group overlapped with that of the sporadic nonfluent variant primary progressive aphasia cohort, although with more posterior cortical involvement, whilst the primary progressive aphasia-not otherwise specified group was strikingly asymmetrical with involvement particularly of the insula and dorsolateral prefrontal cortex but also atrophy of the orbitofrontal cortex and the medial temporal lobes. Whilst there are overlapping symptoms between genetic and sporadic primary progressive aphasia syndromes, there are also distinct features. Future iterations of the primary progressive aphasia consensus criteria should encompass such information with further research needed to understand the earliest features of these disorders, particularly during the prodromal period of genetic disease.

"Please Don't Assess Him to Destruction": The R.A.I.S.E. Assessment Framework for Primary Progressive Aphasia.

Speech-language pathologists (SLPs) assess people with primary progressive aphasia (PPA) through measurements of speech, language, communication, and well-being, with the aims of identifying challenges and strengths, monitoring change, and informing treatment directions and supports. The purpose of this clinical focus article is to highlight the necessity for person-centered assessment specific to PPA and to conceptualize a framework that acknowledges the multifaceted nature of assessment for this population. In this framework, the unique challenges posed by a diagnosis of PPA are addressed with the aim to provide practical guidance for clinicians and to support reflection on current practices. In clinical and research practice, assessment of people with PPA requires an ever-evolving approach that is centered on the client. In this clinical focus article, a discussion-based consensus process was used to synthesize authentic longitudinal experiences of people with PPA to explore assessment approaches, tools, and philosophies. This analysis of person-centered assessment identifies seven essential components of assessment in PPA that set the foundation for the five steps of the R.A.I.S.E. Assessment framework. These components each contribute to a clear definition of assessment that reveals clients' competencies with a strengths-based focus; prioritizes the reciprocity of benefits; promotes dynamic assessment; and recognizes the complexity, evolution of assessment over time, and advocacy. This clinical focus article takes a novel look at assessment in PPA by stepping away from assessment practices that focus on revealing deficits and decline and, instead, provides practical recommendations through the conceptualization of a PPA-specific assessment framework. The R.A.I.S.E. Assessment framework is grounded in principles of uplifting clients through person-centered assessment, keeps pace with best practice in PPA intervention, and contributes to a supportive experience for clients and families in the face of a progressive diagnosis over time.

Access, referral, service provision and management of individuals with primary progressive aphasia: A survey of speech-language therapists in Italy.

In Italy, approximately 650 individuals receive a diagnosis of primary progressive aphasia (PPA) every year. Unfortunately, the frequency with which patients are referred to speech-language services is suboptimal, likely due to skepticism regarding the value of speech-language therapy in the context of neurodegeneration. We conducted a virtual survey of speech and language therapists (SLTs) across Italy, to collect information about the assessment, intervention and management of patients with PPA. To ensure that as many SLTs as possible received the survey, the Italian Federation of SLTs (Federazione Logopedisti Italiani, FLI) aided in disseminating the survey. In total, 336 respondents participated in the online survey, 140 of whom had previous experience with PPA patients. Respondents indicated having seen a total of 428 PPA patients in the previous 24 months (three patients on average, range: 0-40). SLTs who reported never working with PPA identified underdiagnoses, low referral rates and the rarity of the clinical syndrome as major reasons for their lack of experience with PPA. SLTs with experience working with PPA indicated that patients may not have accessed services because of service dysfunction and geographical barriers. Respondents reported using informal interviews during assessments and tests developed for post-stroke aphasia, while impairment-based/restitutive interventions were utilised most often. Findings may serve to inform health policy organisations regarding the current shortcomings and needed recommendations for improving the care of individuals with PPA in Italy. Improving awareness of the utility of rehabilitation among SLTs and other clinical service providers may serve to facilitate access to intervention, which in turn will serve to better support individuals living with PPA. What is already known on the subject Speech and language therapists (SLTs) play a crucial role in the assessment, diagnosis and treatment of people with primary progressive aphasia (PPA). However, the frequency with which individuals with PPA are referred for speech and language services is suboptimal due to skepticism regarding the value of speech and language therapy in the context of neurodegeneration, the scarcity of SLTs with expertise in the treatment of PPA and the lack of awareness of the SLT role amongst referrers. What this paper adds to existing knowledge In recognition of the lack of published information on the provision of speech and language therapy services and clinicians' approaches to the assessment and treatment of individuals with PPA in Italy, we conducted an online survey to evaluate the current referral patterns for speech and language therapy services and to examine the current barriers to access these services for individuals with PPA in Italy. What are the potential or actual clinical implications of this work? The data presented here support that SLTs view treatment as useful for individuals with PPA and other professional figures and may serve to improve access to intervention, which in turn will serve to better support individuals living with PPA. The results highlight the need to inform health policy organisations about current gaps and aid in developing recommendations for improving the care of individuals with PPA, in order to understand how SLTs can best support individuals with PPA and their families.

Quem são os fonoaudiólogos que trabalham com afasia progressiva primária no Brasil? Um estudo de inquérito transversal exploratório

ABSTRACT Primary Progressive Aphasia (PPA) is a progressive language disorder associated with frontotemporal impairment and mainly affects the left hemisphere of the brain. In general, this condition compromises abilities related to comprehension and expression of language. The diagnosis of PPA depends on in-depth knowledge regarding functions of language, neurology, and neuropsychology. Speech and language therapists (SLTs) have a pivotal role in the diagnosis and rehabilitation of PPA. The absence of these professionals involved in the diagnosis and rehabilitation may reflect on the quality of care of people with PPA. Objective: To identify the sociodemographic, educational, and professional practice characteristics of SLTs who work with people with PPA in Brazil. Methods: An online questionnaire was disseminated to reach SLTs across Brazil. The questionnaire collected information regarding sociodemographics, training and education, practice (time, setting, service provision), and sources of referral. Results: The study included 71 participants (95.8% women). Specialization was the most frequent educational level followed by master’s degree, and participants where mainly from the Southeast and South regions of Brazil. Neurologists were the professionals who most referred patients with PPA to SLTs. Finally, SLTs worked primarily in homecare settings and provided mainly individual therapy services. Conclusion: SLTs who work with PPA in Brazil can be characterized mainly as professionals with postgraduate degrees, relatively young, and from the South and Southeast regions of Brazil.

Neuropsychiatric outcomes and caregiver distress in primary progressive aphasia.

In this study, we aimed to outline the neuropsychiatric consequences of primary progressive aphasia (PPA) and to understand how neuropsychiatric symptomatology affects distress in caregivers. The Neuropsychiatric Inventory (NPI) including the distress index (NPI-Distress) was used. Additional information about the caregiver burden was obtained using Zarit Burden Interview (ZBI). NPI, NPI-Distress, and ZBI data from 17 patients with a clinical diagnosis of PPA were compared with 10 stroke aphasia patients. Neuropsychiatric symptomatology was investigated based on three clusters; Mood, Frontal/Comportmental, and Psychotic/Disruptive. Additionally, the Activities of Daily Living Questionnaire (ADLQ) was used to outline the functional impairment. Twelve healthy controls were included to compare the neurocognitive test scores with PPA and stroke aphasia groups. A greater number of neuropsychiatric symptoms were observed in the PPA group compared to the stroke aphasia group. The number of symptoms in Mood, and Frontal/Comportmental clusters were greater than the number of symptoms in Psychotic/Disruptive clusters in the PPA group, whereas no significant relationship between the number of symptoms and symptom clusters was found in the stroke aphasia group. In the PPA group, a strong correlation was found between the NPI-Frequency×Severity scores and the NPI-Distress scores. Moreover, the NPI-Distress scores in the PPA group strongly correlated with the ZBI scores. Scores for anxiety, irritability/lability, and apathy had a stronger correlation with the NPI-Distress scores compared to the other NPI symptoms. The Communication subscale was the most impaired domain in the PPA group. Travel, and Employment and Recreation subscales showed greater functional impairment in the stroke aphasia group compared to the PPA group. Neuropsychiatric symptoms in PPA in our study were more frequent than previously reported. Furthermore, the distress index of the NPI was not only correlated with the severity of the neuropsychiatric symptoms but also reflected the overall burden on the caregivers in the PPA group.

The affective, behavioural, and cognitive reactions to a diagnosis of Primary Progressive Aphasia: A qualitative descriptive study.

Receiving a diagnosis of neurodegenerative disorder is life changing. Primary progressive aphasia is one such disease. Understanding how receiving this diagnosis impacts on individuals may help plan support services. However, limited qualitative research from the perspectives of people with Primary Progressive Aphasia are available for suitable care planning. Current literature primarily focuses on experiences of family members. The present study aims to fill this gap by examining the affective, behavioural, and cognitive experiences of people with Primary Progressive Aphasia. Semi-structured interviews were conducted with six participants with PPA. A qualitative descriptive approach was used to describe responses from participants on: (i) what they experienced prior to receiving their diagnosis; (ii) their experience of receiving the diagnosis; and (iii) how they were living with their PPA. Verbatim transcripts were analysed using thematic analysis to identify main themes. Analysis revealed a superordinate theme of Multifaceted Grief with subthemes described in sequence of research questions posed, representing the three phases of Pre-Diagnosis, Time of Diagnosis, and Post-Diagnosis. Themes collectively revealed participants' ongoing experience of loss in dealing with the evolving challenges of Primary Progressive Aphasia. Experiences of loss emerged with descriptions of feelings, thoughts, and limitations in relation to changes imposed by the illness, impacting daily activities and life roles central to participants' pre-diagnosis sense of self. Participants' affective, behavioural and cognitive reactions to their Primary Progressive Aphasia diagnosis marks the onset of Multifaceted Grief borne of loss of communication and cognition. Participants expressed a need for information regarding a possible Primary Progressive Aphasia trajectory and support to enable a successful transition as their disease progressed. Collaborative engagement between speech pathologists and people with Primary Progressive Aphasia incorporates addressing all levels of the International Classification of Functioning and Health by considering neurological, psychological, and psychosocial experiences of the person with the diagnosis.

Research trends of the neuroimaging in aphasia: A bibliometric analysis and visualization analysis from 2004 to 2021

ObjectivesTo review the current research status of the neuroimaging of aphasia, and reveal the hotspots and frontiers of research in this field.MethodsWe searched articles related to the neuroimaging research on aphasia since Web of Science (WOS) database construction and extracted the data. CiteSpace and VOSviewer were used for the country/institution analysis, journal analysis, discipline analysis, burst keyword analysis and cited-reference cluster analysis.ResultsOf the studies retrieved from WOS, 2922 studies that related to the neuroimaging of aphasia were screened and finally included 2799 articles for research. The United States of America and University of California San Francisco were the main countries and institutions in this field. Brain had the highest impact factor in both published and cited journals. Through the discipline and topic analysis of this field, the most common category was Neurosciences and Neurology. The keyword with the strongest citation strength was “functional connectivity,” and the recent burst keywords were “functional connectivity” and “network.” The co-citation network showed seven clusters greater than 100. Among the top 5 clusters, the most recently formed cluster, Cluster #2 (progressive supranuclear palsy), had an average year of 2017. The literature in the top 5 clusters mainly focused on 3 aspects, specifically, the discovery of language processing models, injury and recovery mechanisms of post-stroke aphasia (PSA), and diagnosis of primary progressive aphasia (PPA) variants.ConclusionThe results of this bibliometric study revealed the following three research hotspots in the neuroimaging of aphasia: clarifying the connotation of the most recognized language processing model, the dual-stream model, exploring the injury mechanism based on the dual-stream model and the recovery mechanism involving the left and right hemispheres of PSA, and determining the diagnostic criteria for PPA variants. A major research trend is to combine new neuroimaging technology, such as PET tracer technology, to realize the visual presentation of disease-specific proteins to improve the pathological diagnostic criteria of PPA variants. Accordingly, a visualized analysis of literature that uses CiteSpace provides a more rapid, repeatable and flexible method, which is more conducive to capturing research hotspots and emerging trends.

The course of primary progressive aphasia diagnosis: a cross-sectional study

BackgroundThe primary progressive aphasia (PPA) diagnosis trajectory is debated, as several changes in diagnosis occur during PPA course, due to phenotype evolution from isolated language alterations to global cognitive impairment.The goal of the present study, based on a French cohort, was to describe the demographics and the evolution of subjects with (PPA) in comparison with Alzheimer’s disease (AD) on a period of 7 years.MethodsWe conducted a repeated cross-sectional study. The study population comprised individuals with PPA and AD diagnosis (N=167,191) from 2010 to 2016 in the French National data Bank (BNA). Demographic variables, MMSE scores, diagnosis status at each visit and prescribed treatments were considered.ResultsFrom 2010 to 2016, 5186 patients were initially diagnosed with PPA, 162,005 with AD. Compared to AD subjects, significant differences were found concerning age (younger at first diagnosis for PPA), gender (more balanced in PPA), education level (higher in PPA) and MMSE score (higher of 1 point in PPA).Percentage of pending diagnosis, delay between first consultation and first diagnosis and the number of different diagnoses before the diagnosis of interest were significantly higher in PPA group compared to AD group. Pharmacological and non-pharmacological treatments were significatively more recommended following PPA than AD diagnosis.ConclusionThis study improves the knowledge of PPA epidemiology and has the potential to help adopting appropriate public health service policies. It supports the hypothesis that PPA is diagnosed later than AD. The PPA diagnosis increases the prescription of non-pharmacological treatments, especially speech and language therapy (SLT) that is the main treatment available and most effective when at the initial stage.Trial registrationClinicalTrials.gov identifier NCT03687112

The possibilities of differential diagnosis of primary progressive aphasia

The authors describe a clinical case demonstrating the difficulties of diagnosing primary progressive aphasia, the need for a differential diagnosis with a logopenic variant of Alzheimer's disease. The data of a clinical, neuropsychological study with a detailed instrumental and diagnostic search, including data from cerebrospinal fluid, positron emission tomography-CT, MRI, electroencephalography with cognitive loads, are presented. The article focuses on the widespread use of various diagnostic scales based on the international diagnostic criteria.

Primary progressive aphasias: clinical and genetic heterogeneity and diagnostic difficulties

This systematic review describes primary progressive aphasia (PPA) variants and includes the authors' own clinical observations. Over 20 genes have now been identified, with mutations that are directly involved in the development of the behavioural variant of frontotemporal dementia, as well as other forms of PPA. Pathomorphological markers of Alzheimer's disease were identified in 76% of cases of logopenic PPA, while signs of frontotemporal dementia associated with TDP-43 were identified in 80% of cases of the semantic variant, and those associated with TDP-43/tau were identified in 64% of cases of agrammatic PPA. The clinical diagnosis of PPA is based on a history of long-term, progressive speech disturbances and identifying a particular variant: agrammatic, semantic or logopenic. The primary variant of the speech disorder cannot be identified in approximately 30% of cases. The focus should be on the main and additional clinical signs (presence of agrammatism, object naming, word comprehension, preserved repetition), as well as neuroimaging (presence of asymmetrical frontal and/or temporal lobe atrophy).
 The article also provides key aspects of differential diagnosis of the PPA variants, and puts forth a stepwise diagnostic algorithm. It examines features of PPA progression, with possible development of corticobasal syndrome, illustrated by a clinical case. A dissociation between neuroimaging findings and clinical disease variant is also demonstrated to be possible. Different neuropsychological assessments of patients with aphasia and methods of determining the severity of speech dysfunction are presented. Standardized aphasia assessment tools and the adapted PPA severity scale are provided.